HIV AIDS natural history, complications, and prognosis: Difference between revisions

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Latest revision as of 22:30, 20 September 2021

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2] ; Alejandro Lemor, M.D. [3]

Overview

There is currently no cure for HIV/AIDS. HIV infection leads to progressive decline in CD4+ T-lymphocyte count increasing the risk for opportunistic infections and malignancies. Despite having a variable rate of progression determined by specific host and viral factors, the median time from infection to the development of AIDS ranges from 8 to 10 years among untreated individuals.^[1] With the advent of highly active antiretroviral therapy (HAART), both morbidity and mortality have dramatically decreased. Survival and the rate of CD4-count recovery is influenced by age, baseline CD4 cell count, baseline viral load and initial and sustained viral suppression.^[2] In areas where HAART is widely available, the development of HAART as effective therapy for HIV infection and AIDS reduced the death rate from this disease by 80%, and raised the life expectancy for a newly-diagnosed HIV-infected person to near normal (assuming full compliance to HAART).^[3] HIV infection makes individuals highly susceptible to severe opportunistic infections and neoplastic disease. Major complications of HIV/AIDS include Pneumocystis jirovecii pneumonia, disseminated Mycobacterium avium complex infection, cryptococcal meningitis, cytomegalovirus retinitis, Kaposi sarcoma, and primary CNS lymphoma.

Natural History

In the early days of the HIV epidemic, knowledge about the natural history of HIV accrued rapidly. However, the widespread use of effective antiretroviral therapy (ART) brought a shift in focus of the research community away from studies of natural history to those of treated infection.^[4] HIV infection leads to progressive decline in CD4+ T-lymphocyte count increasing the risk for opportunistic infections and malignancies. Despite having a variable rate of progression determined by specific host and viral factors, the median time from infection to the development of AIDS ranges from 8 to 10 years among untreated individuals.^[1] With the advent of highly active antiretroviral therapy (HAART), both morbidity and mortality have dramatically decreased. Survival and the rate of CD4-count recovery is influenced by age, baseline CD4 cell count, baseline viral load and initial and sustained viral suppression.^[2]

Disease Progression

Natural history of untreated HIV - By Sigve - Own work, CC0, https://commons.wikimedia.org/w/index.php?curid=15383502

Acute HIV syndrome

Approximately half of patients that acquire HIV develop a mononucleosis-like syndrome within 3-6 weeks during which the viral titers are very elevated. Common symptoms include acute but brief and nonspecific influenza-like retroviral syndrome that can include fever, malaise, lymphadenopathy, pharyngitis, arthritis, or skin rash.^[5] This causes a rapid drop in CD4 T-Cell count as these cells are the primary host for viral replication. Within several weeks patients mount a strong immune response to the virus that causes a drop in the viral titers. However, this response is not adequate to completely suppress viral replication. Although viremia may become undetectable, replication persists in the lymphoid organs. Although a significant number of patients do not have an acute HIV syndrome, these processes do occur albeit without symptoms.^[6]

Clinical Latency

This period is sometimes called asymptomatic HIV infection or chronic HIV infection. After the initial phase, the majority of patients with HIV develop a clinical latency period that lasts several years. During this period, all patients have a progressive decline in immune status and gradual depletion of CD4 T-cells. This period does not represent a true microbiological or pathological latency, but rather defines a time period without clinically manifest disease. People who are on highly active antiretroviral therapy (HAART) may live with clinical latency for several decades.^[6]

Clinically Apparent Disease (AIDS)

The eventual outcome of most HIV infections is gradual immune system deterioration resulting in AIDS. Clinically apparent disease is classically diagnosed following an AIDS-defining illness i.e. an opportunistic infection or neoplasm that demonstrates a significant compromise of the immune system. Another diagnostic sign, although not strictly clinical, is the decline of CD4 T-cell count below 200 cells/mm³. Without treatment, individuals diagnosed with AIDS may survive approximately 1-3 years.^[6]

Distinct Patterns of Progression

The natural course of untreated HIV infection varies widely. The past decade has seen considerable interest in the identification of subgroups of HIV-positive persons who exhibit distinct patterns of disease progression:^[4]

Long-term nonprogressors (LTNP) are individuals who remain asymptomatic for a prolonged period of time off ART with a high CD4 cell count. Although it is widely reported that 1–5% of the HIV-positive population are LTNP, these estimates are complicated by the fact that there is no standardized definition of a LTNP, and thus definitions used (and the way in which they are applied, particularly in the presence of varying follow-up and irregularly measured CD4 cell counts) differ widely. LTNP status can be lost, and thus the reported prevalence of LTNP within a study will depend on the required period of follow-up. Predictors of loss of LTNP status are a high baseline HIV DNA level and a more rapid increase in HIV DNA over the first year of follow-up, suggesting the presence of ongoing (but low-grade) viral replication. Indeed, HIV RNA levels in plasma increased by 0.04 log10 copies/ml per year over the first 8 years after diagnosis. As such, it is likely that virtually all HIV-positive persons will eventually experience disease progression if left untreated.^[4]

Elite controllers or viral controllers are individuals who are able to suppress HIV replication to such an extent that viral load levels remain undetectable in the absence of ART. As with LTNP, several studies have attempted to identify factors associated with elite controller status. Loss of naive CD4 T cells seems to be a universal feature of elite controllers, despite the ability of such individuals to maintain undetectable viral loads. However, CD4 naive lymphocytes from elite controllers tend to be less susceptible to HIV infection than such lymphocytes from progressors or uninfected individuals. This specific feature was linked with upregulation of a cellular kinase (p21). HIV-specific CD4 activation is a hallmark of viral control but, many other host factors have been linked with this phenotype, including cellular restriction factors such as APOBEC, tetherin, and SAMHD1. In addition, several viral factors may also play a role, including deletions or mutations with the viral genes that may have an impact on the ability of the virus to replicate. ^[4]

Complications

HIV infection makes individuals highly susceptible to severe opportunistic infections and neoplastic disease. The following complications are classically observed among patients with significant immunocompromise and rarely manifest among patients with a CD4 count greater than 350 cells/mm³.

Prognosis

Without treatment, the net median survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype, and the median survival rate after diagnosis of AIDS in resource-limited settings where treatment is not available ranges between 6 and 19 months, depending on the study.^[7] In areas where it is widely available, the development of HAART as effective therapy for HIV infection and AIDS reduced the death rate from this disease by 80%, and raised the life expectancy for a newly-diagnosed HIV-infected person to near normal (assuming full compliance to HAART).^[8]

References

↑ ^1.0 ^1.1 Vergis EN, Mellors JW (2000). "Natural history of HIV-1 infection". Infect Dis Clin North Am. 14 (4): 809–25, v–vi. PMID 11144640.
↑ ^2.0 ^2.1 Giles M, Workman C (2009). "Clinical manifestations and the natural history of HIV" (PDF). Australian Society for HIV Management: 125–32. ISBN 9781920773571.
↑ Knoll B, Lassmann B, Temesgen Z (2007). "Current status of HIV infection: a review for non-HIV-treating physicians". Int J Dermatol. 46 (12): 1219–28. doi:10.1111/j.1365-4632.2007.03520.x. PMID 18173512.
↑ ^4.0 ^4.1 ^4.2 ^4.3 Sabin CA, Lundgren JD (2013). "The natural history of HIV infection". Curr Opin HIV AIDS. 8 (4): 311–7. doi:10.1097/COH.0b013e328361fa66. PMC 4196796. PMID 23698562.CS1 maint: PMC format (link)
↑ Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I; et al. (2021). "Sexually Transmitted Infections Treatment Guidelines, 2021". MMWR Recomm Rep. 70 (4): 1–187. doi:10.15585/mmwr.rr7004a1. PMC 8344968 Check |pmc= value (help). PMID 34292926 Check |pmid= value (help).
↑ ^6.0 ^6.1 ^6.2 Pantaleo G, Graziosi C, Fauci AS (1993). "New concepts in the immunopathogenesis of human immunodeficiency virus infection". N Engl J Med. 328 (5): 327–35. doi:10.1056/NEJM199302043280508. PMID 8093551.
↑ Template:Cite paper
↑ Knoll B, Lassmann B, Temesgen Z (2007). "Current status of HIV infection: a review for non-HIV-treating physicians". Int J Dermatol. 46 (12): 1219–28. doi:10.1111/j.1365-4632.2007.03520.x. PMID 18173512.

Template:WH Template:WS

[pmid11144640-1] 1.0 ^1.1 Vergis EN, Mellors JW (2000). "Natural history of HIV-1 infection". Infect Dis Clin North Am. 14 (4): 809–25, v–vi. PMID 11144640.

[aust-2] 2.0 ^2.1 Giles M, Workman C (2009). "Clinical manifestations and the natural history of HIV" (PDF). Australian Society for HIV Management: 125–32. ISBN 9781920773571.

[3] Knoll B, Lassmann B, Temesgen Z (2007). "Current status of HIV infection: a review for non-HIV-treating physicians". Int J Dermatol. 46 (12): 1219–28. doi:10.1111/j.1365-4632.2007.03520.x. PMID 18173512.

[pmid23698562-4] 4.0 ^4.1 ^4.2 ^4.3 Sabin CA, Lundgren JD (2013). "The natural history of HIV infection". Curr Opin HIV AIDS. 8 (4): 311–7. doi:10.1097/COH.0b013e328361fa66. PMC 4196796. PMID 23698562.CS1 maint: PMC format (link)

[pmid34292926-5] Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I; et al. (2021). "Sexually Transmitted Infections Treatment Guidelines, 2021". MMWR Recomm Rep. 70 (4): 1–187. doi:10.15585/mmwr.rr7004a1. PMC 8344968 Check |pmc= value (help). PMID 34292926 Check |pmid= value (help).

[pmid8093551-6] 6.0 ^6.1 ^6.2 Pantaleo G, Graziosi C, Fauci AS (1993). "New concepts in the immunopathogenesis of human immunodeficiency virus infection". N Engl J Med. 328 (5): 327–35. doi:10.1056/NEJM199302043280508. PMID 8093551.

[7] Template:Cite paper

[8] Knoll B, Lassmann B, Temesgen Z (2007). "Current status of HIV infection: a review for non-HIV-treating physicians". Int J Dermatol. 46 (12): 1219–28. doi:10.1111/j.1365-4632.2007.03520.x. PMID 18173512.

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@@ Line 1: / Line 1: @@
+__NOTOC__
 {{AIDS}}
-{{CMG}}
+{{CMG}}; {{AE}} {{Ammu}} ; {{AL}}
 ==Overview==
-'''Acquired immune deficiency syndrome  ''' ('''AIDS''') is a [[syndrome|collection of symptoms and infections]] resulting from the specific damage to the [[immune system]] caused by the [[HIV|human immunodeficiency virus]] (HIV) in humans,<ref>{{cite web
+There is currently no cure for HIV/[[AIDS]].  HIV infection leads to progressive decline in CD4+ T-lymphocyte count increasing the risk for opportunistic infections and malignancies. Despite having a variable rate of progression determined by specific host and viral factors, the median time from infection to the development of AIDS ranges from 8 to 10 years among untreated individuals.<ref name="pmid11144640">{{cite journal| author=Vergis EN, Mellors JW| title=Natural history of HIV-1 infection. | journal=Infect Dis Clin North Am | year= 2000 | volume= 14 | issue= 4 | pages= 809-25, v-vi | pmid=11144640 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11144640  }} </ref> With the advent of highly active antiretroviral therapy (HAART), both morbidity and mortality have dramatically decreased. Survival and the rate of CD4-count recovery is influenced by age, baseline CD4 cell count, baseline viral load and initial and sustained viral suppression.<ref name="aust">{{cite journal| author=Giles M, Workman C| title=Clinical manifestations and the natural history of HIV | journal=Australian Society for HIV Management | year= 2009 | pages= 125-32 | isbn=9781920773571 | url=http://www.ashm.org.au/images/Publications/Monographs/HIV_Management_Australasia/HIV-Management-Australia-2009.pdf  }} </ref>  In areas where HAART is widely available, the development of [[HAART]] as effective therapy for HIV infection and AIDS reduced the death rate from this disease by 80%, and raised the life expectancy for a newly-diagnosed HIV-infected person to near normal (assuming full compliance to HAART).<ref>{{cite journal |journal= Int J Dermatol |date=2007 |volume=46 |issue=12 |pages=1219–28 |title= Current status of HIV infection: a review for non-HIV-treating physicians |author= Knoll B, Lassmann B, Temesgen Z |pmid=18173512 |doi=10.1111/j.1365-4632.2007.03520.x |pmid=18173512}}</ref>  HIV infection makes individuals highly susceptible to severe opportunistic infections and neoplastic disease. Major complications of HIV/AIDS include ''[[Pneumocystis jirovecii]]'' pneumonia, disseminated [[Mycobacterium avium complex]] infection, [[Cryptococcus|cryptococcal meningitis]], [[cytomegalovirus]] retinitis, [[Kaposi sarcoma]], and [[primary CNS lymphoma]].
-|url=http://www.niaid.nih.gov/Publications/hivaids/hivaids.htm
-|title=The Relationship Between the Human Immunodeficiency Virus and the Acquired Immunodeficiency Syndrome |publisher= NIAID
-|accessdate=2008-03-10}}</ref> and similar viruses in other species ([[Simian immunodeficiency virus|SIV]], [[Feline immunodeficiency virus|FIV]], etc.)
 ==Natural History==
+In the early days of the HIV epidemic, knowledge about the natural history of HIV accrued rapidly. However, the widespread use of effective antiretroviral therapy (ART) brought a shift in focus of the research community away from studies of natural history to those of treated infection.<ref name="pmid23698562">{{cite journal| author=Sabin CA, Lundgren JD| title=The natural history of HIV infection. | journal=Curr Opin HIV AIDS | year= 2013 | volume= 8 | issue= 4 | pages= 311-7 | pmid=23698562 | doi=10.1097/COH.0b013e328361fa66 | pmc=PMC4196796 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23698562  }} </ref>  HIV infection leads to progressive decline in CD4+ T-lymphocyte count increasing the risk for opportunistic infections and malignancies. Despite having a variable rate of progression determined by specific host and viral factors, the median time from infection to the development of AIDS ranges from 8 to 10 years among untreated individuals.<ref name="pmid11144640">{{cite journal| author=Vergis EN, Mellors JW| title=Natural history of HIV-1 infection. | journal=Infect Dis Clin North Am | year= 2000 | volume= 14 | issue= 4 | pages= 809-25, v-vi | pmid=11144640 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11144640  }} </ref> With the advent of highly active antiretroviral therapy (HAART), both morbidity and mortality have dramatically decreased. Survival and the rate of CD4-count recovery is influenced by age, baseline CD4 cell count, baseline viral load and initial and sustained viral suppression.<ref name="aust">{{cite journal| author=Giles M, Workman C| title=Clinical manifestations and the natural history of HIV | journal=Australian Society for HIV Management | year= 2009 | pages= 125-32 | isbn=9781920773571 | url=http://www.ashm.org.au/images/Publications/Monographs/HIV_Management_Australasia/HIV-Management-Australia-2009.pdf  }} </ref>
-Currently there is no cure for AIDS but taking treatment dramatically increased the amount of time people with HIV remain alive.
+===Disease Progression===
-Research continues in the areas of drug treatments and vaccine development. Unfortunately, HIV medications are not always available in the developing world, where the bulk of cases now occur.
+[[File:HIV_natural_history.png|thumb|700px|center|Natural history of untreated HIV - By Sigve - Own work, CC0, https://commons.wikimedia.org/w/index.php?curid=15383502]]
+====Acute HIV syndrome====
+Approximately half of patients that acquire HIV develop a mononucleosis-like syndrome within 3-6 weeks during which the viral titers are very elevated. Common symptoms include [[acute]] but brief and nonspecific [[influenza]]-like [[retroviral syndrome]] that can include [[fever]], [[malaise]], [[lymphadenopathy]], [[pharyngitis]], [[arthritis]], or [[skin rash]].<ref name="pmid34292926">{{cite journal| author=Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I | display-authors=etal| title=Sexually Transmitted Infections Treatment Guidelines, 2021. | journal=MMWR Recomm Rep | year= 2021 | volume= 70 | issue= 4 | pages= 1-187 | pmid=34292926 | doi=10.15585/mmwr.rr7004a1 | pmc=8344968 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34292926  }} </ref> This causes a rapid drop in CD4 T-Cell count as these cells are the primary host for viral replication. Within several weeks patients mount a strong immune response to the virus that causes a drop in the viral titers. However, this response is not adequate to completely suppress viral replication. Although viremia may become undetectable, replication persists in the lymphoid organs. Although a significant number of patients do not have an acute HIV syndrome, these processes do occur albeit without symptoms.<ref name="pmid8093551">{{cite journal| author=Pantaleo G, Graziosi C, Fauci AS| title=New concepts in the immunopathogenesis of human immunodeficiency virus infection. | journal=N Engl J Med | year= 1993 | volume= 328 | issue= 5 | pages= 327-35 | pmid=8093551 | doi=10.1056/NEJM199302043280508 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8093551  }} </ref>
-==Prognosis==
+====Clinical Latency====
-Without treatment, the net median survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype, and the median survival rate after diagnosis of AIDS in resource-limited settings where treatment is not available ranges between 6 and 19 months, depending on the study.<ref>{{cite paper |title= Progression and mortality of untreated HIV-positive individuals living in resource-limited settings: update of literature review and evidence synthesis |author= Zwahlen M, Egger M |url=http://data.unaids.org/pub/Periodical/2006/zwahlen_unaids_hq_05_422204_2007_en.pdf |format=PDF |date=2006 |accessdate=2008-03-19 |version= UNAIDS Obligation HQ/05/422204}}</ref> In areas where it is widely available, the development of [[HAART]] as effective therapy for HIV infection and AIDS reduced the death rate from this disease by 80%, and raised the life expectancy for a newly-diagnosed HIV-infected person to about 20 years.<ref>{{cite journal |journal= Int J Dermatol |date=2007 |volume=46 |issue=12 |pages=1219–28 |title= Current status of HIV infection: a review for non-HIV-treating physicians |author= Knoll B, Lassmann B, Temesgen Z |pmid=18173512 |doi=10.1111/j.1365-4632.2007.03520.x |pmid=18173512}}</ref>
+This period is sometimes called asymptomatic HIV infection or chronic HIV infection. After the initial phase, the majority of patients with HIV develop a clinical latency period that lasts several years. During this period, all patients have a progressive decline in immune status and gradual depletion of CD4 T-cells. This period does not represent a true microbiological or pathological latency, but rather defines a time period without clinically manifest disease. People who are on highly active antiretroviral therapy (HAART) may live with clinical latency for several decades.<ref name="pmid8093551">{{cite journal| author=Pantaleo G, Graziosi C, Fauci AS| title=New concepts in the immunopathogenesis of human immunodeficiency virus infection. | journal=N Engl J Med | year= 1993 | volume= 328 | issue= 5 | pages= 327-35 | pmid=8093551 | doi=10.1056/NEJM199302043280508 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8093551  }} </ref>
-==Complications==
+====Clinically Apparent Disease (AIDS)====
-HIV infection weakens patients immune system, making them highly susceptible to variety of infections and certain types of cancers.
+The eventual outcome of most HIV infections is gradual immune system deterioration resulting in AIDS. Clinically apparent disease is classically diagnosed following an AIDS-defining illness i.e. an opportunistic infection or neoplasm that demonstrates a significant compromise of the immune system. Another diagnostic sign, although not strictly clinical, is the decline of CD4 T-cell count below 200 cells/mm<sup>3</sup>. Without treatment, individuals diagnosed with AIDS may survive approximately 1-3 years.<ref name="pmid8093551">{{cite journal| author=Pantaleo G, Graziosi C, Fauci AS| title=New concepts in the immunopathogenesis of human immunodeficiency virus infection. | journal=N Engl J Med | year= 1993 | volume= 328 | issue= 5 | pages= 327-35 | pmid=8093551 | doi=10.1056/NEJM199302043280508 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8093551  }} </ref>
-===1. Infections common to HIV/AIDS===
-* [[Tuberculosis]] (TB).
-* [[Salmonellosis]].
-* [[Cytomegalovirus]] (CMV).
-* [[Candidiasis]].
-* [[Cryptococcus|Cryptococcal meningitis]].
-* [[Toxoplasmosis]].
-* [[Cryptosporidiosis]].
-===2. Cancers common to HIV/AIDS===
+===Distinct Patterns of Progression===
-*  '''2.A. [[Kaposi's sarcoma]]'''.
+''The natural course of untreated HIV infection varies widely. The past decade has seen considerable interest in the identification of subgroups of HIV-positive persons who exhibit distinct patterns of disease progression:''<ref name="pmid23698562">{{cite journal| author=Sabin CA, Lundgren JD| title=The natural history of HIV infection. | journal=Curr Opin HIV AIDS | year= 2013 | volume= 8 | issue= 4 | pages= 311-7 | pmid=23698562 | doi=10.1097/COH.0b013e328361fa66 | pmc=PMC4196796 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23698562  }} </ref>
-AIDS-associated Kaposi sarcoma presents with cutaneous [[lesion]]s that begin as one or several red to purple-red [[macule]]s, rapidly progressing to [[papule]]s, [[Nodule_(dermatology)|nodule]]s, and [[plaque_(dermatology)|plaque]]s, with a predilection for the head, neck, trunk, and [[mucous membrane]]s.<ref name="Andrews">James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. ISBN 0-7216-2921-0.</ref>
-AIDS-associated Kaposi sarcoma simulated the greatest interest as one of the first illnesses associated with [[AIDS]]. Different from the classic form of [[Kaposi sarcoma]], Tumors usually appear on the [[head]], [[back]], [[neck]], [[muscular palate]] and the area of the [[gingiva]].
+*'''Long-term nonprogressors (LTNP)''' are individuals who remain asymptomatic for a prolonged period of time off ART with a high CD4 cell count. Although it is widely reported that 1–5% of the HIV-positive population are LTNP, these estimates are complicated by the fact that there is no standardized definition of a LTNP, and thus definitions used (and the way in which they are applied, particularly in the presence of varying follow-up and irregularly measured CD4 cell counts) differ widely.  LTNP status can be lost, and thus the reported prevalence of LTNP within a study will depend on the required period of follow-up. Predictors of loss of LTNP status are a high baseline HIV DNA level and a more rapid increase in HIV DNA over the first year of follow-up, suggesting the presence of ongoing (but low-grade) viral replication. Indeed, HIV RNA levels in plasma increased by 0.04 log10 copies/ml per year over the first 8 years after diagnosis. As such, it is likely that virtually all HIV-positive persons will eventually experience disease progression if left untreated.<ref name="pmid23698562">{{cite journal| author=Sabin CA, Lundgren JD| title=The natural history of HIV infection. | journal=Curr Opin HIV AIDS | year= 2013 | volume= 8 | issue= 4 | pages= 311-7 | pmid=23698562 | doi=10.1097/COH.0b013e328361fa66 | pmc=PMC4196796 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23698562  }} </ref>
-In more advanced cases, they can be found in the stomach and intestines, the lymph nodes, and the lungs. KS-AIDS was first described in 1981 by three separate groups, most notably by [[Robert A. Schwartz]] and his collaborators at the University of Arizona.<ref> {{cite journal | title = Kaposi's sarcoma presenting in a homosexual man — a new and striking phenomenon | journal = Ariz Med | year = 1994 | first = Robert A. | last = Schwartz | coauthors = SP Borkovic | volume = 38 | issue = 12 | pages = 902–4| id = | accessdate = 2010-07-29}}</ref><ref> {{cite book | last1 = Hausen | first1 = Harald Zur | authorlink1 = Harald Zur Hausen | title = Infections Causing Human Cancer | chapter = Rhadinoviruses | publisher = Wiley-VCH | year = 2006 | location = Weinheim | accessdate = 2010-07-29}}</ref><ref> {{cite book | last1 = Drabell | first1 = Fredrick G | title = New Topics in Cancer Research | chapter = Kaposi's Sarcoma and Renal Diseases | publisher = Nova Biomedical Books | year = 2006 | location = New York | accessdate = 2010-07-29}}</ref>
+*'''Elite controllers''' or '''viral controllers''' are individuals who are able to suppress HIV replication to such an extent that viral load levels remain undetectable in the absence of ART. As with LTNP, several studies have attempted to identify factors associated with elite controller status. Loss of naive CD4 T cells seems to be a universal feature of elite controllers, despite the ability of such individuals to maintain undetectable viral loads. However, CD4 naive lymphocytes from elite controllers tend to be less susceptible to HIV infection than such lymphocytes from progressors or uninfected individuals. This specific feature was linked with upregulation of a cellular kinase (p21). HIV-specific CD4 activation is a hallmark of viral control but, many other host factors have been linked with this phenotype, including cellular restriction factors such as APOBEC, tetherin, and SAMHD1. In addition, several viral factors may also play a role, including deletions or mutations with the viral genes that may have an impact on the ability of the virus to replicate. <ref name="pmid23698562">{{cite journal| author=Sabin CA, Lundgren JD| title=The natural history of HIV infection. | journal=Curr Opin HIV AIDS | year= 2013 | volume= 8 | issue= 4 | pages= 311-7 | pmid=23698562 | doi=10.1097/COH.0b013e328361fa66 | pmc=PMC4196796 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23698562  }} </ref>
-* '''2.B. [[AIDS-related lymphoma|Lymphomas]].'''
+==Complications==
-To read more about AIDS-related Lymphome, click [[AIDS-related lymphoma|'''here''']].
+HIV infection makes individuals highly susceptible to severe opportunistic infections and neoplastic disease. The following complications are classically observed among patients with significant immunocompromise and rarely manifest among patients with a CD4 count greater than 350 cells/mm<sup>3</sup>.
+===1. Infections===
+* ''[[Pneumocystis jirovecii]]'' pneumonia
+* [[Tuberculosis]]
+* Disseminated [[Mycobacterium avium complex]]
+* [[Salmonellosis]] (Septicemia)
+* [[Cytomegalovirus]] retinitis
+* [[Candidiasis]]
+* [[Cryptococcus|Cryptococcal meningitis]]
+* Cerebral [[Toxoplasmosis]]
+* Cryptococcal meningitis
+* Disseminated [[Coccidiomycosis]]
+* Disseminated [[Histoplasmosis]]
+* [[Cryptosporidiosis]]
+* Isosporiasis
-===3. Other complications===
+===2. Cancers===
+* [[Kaposi Sarcoma]]
+* [[AIDS-related lymphoma]]s
+:*[[Non-Hodgkin's Lymphoma]]
+:*[[Hodgkin's Lymphoma]]
+:*[[Primary CNS Lymphoma]]
+:*Burkitt's Lymphoma
+:*Large B-cell Lymphoma
+* Invasive [[cervical cancer]]
+* Invasive [[anal cancer]]
-* '''[[Wasting syndrome]]'''.
+===3. Other Complications===
-* '''Neurological complications.'''
-Although HIV doesn't appear to invade the neuron, it can still cause neurological symptoms such as:
-:* [[Confusion]]
-:* Forgetfulness
-:* [[Depression]]
-:* [[Anxiety]]
-One of the most common neurological complications in AIDS patient is AIDS dementia complex, to read more about it, click [[AIDS dementia complex|'''here''']]
-* '''Stigma associated with AIDS'''
-[[Image:Saigon AIDS Sign.jpg|100px|left|AIDS Awareness Sign. Ho Chi Minh City, Vietnam (August 2005).]]
-AIDS stigma exists around the world in a variety of ways, including ostracism, rejection, discrimination and avoidance of HIV infected people; compulsory HIV testing without prior [[consent]] or protection of confidentiality; violence against HIV infected individuals or people who are perceived to be infected with HIV; and the [[quarantine]] of HIV infected individuals.<ref name=UNAIDS2006Ch4>{{
-cite book
+* [[HIV associated nephropathy]]
-| publisher =[[Joint United Nations Programme on HIV/AIDS|UNAIDS]]
+* [[HIV induced pericarditis]]
-| year = 2006
+* HIV-associated wasting syndrome
-| title = 2006 Report on the global AIDS epidemic
+* [[Aortitis]]
-| chapter = The impact of AIDS on people and societies
+* [[AIDS dementia complex]]
-| chapterurl = http://data.unaids.org/pub/GlobalReport/2006/2006_GR_CH04_en.pdf
+* Lymphoid interstitial pneumonia
-| accessdate = 2006-06-14
-| format= PDF
-}}</ref> Stigma-related violence or the fear of violence prevents many people from seeking HIV testing, returning for their results, or securing treatment, possibly turning what could be a manageable chronic illness into a death sentence and perpetuating the spread of HIV.<ref name=Ogden>{{
+==Prognosis==
+Without treatment, the net median survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype, and the median survival rate after diagnosis of AIDS in resource-limited settings where treatment is not available ranges between 6 and 19 months, depending on the study.<ref>{{cite paper |title= Progression and mortality of untreated HIV-positive individuals living in resource-limited settings: update of literature review and evidence synthesis |author= Zwahlen M, Egger M |url=http://data.unaids.org/pub/Periodical/2006/zwahlen_unaids_hq_05_422204_2007_en.pdf |format=PDF |date=2006 |accessdate=2008-03-19 |version= UNAIDS Obligation HQ/05/422204}}</ref> In areas where it is widely available, the development of [[HAART]] as effective therapy for HIV infection and AIDS reduced the death rate from this disease by 80%, and raised the life expectancy for a newly-diagnosed HIV-infected person to near normal (assuming full compliance to HAART).<ref>{{cite journal |journal= Int J Dermatol |date=2007 |volume=46 |issue=12 |pages=1219–28 |title= Current status of HIV infection: a review for non-HIV-treating physicians |author= Knoll B, Lassmann B, Temesgen Z |pmid=18173512 |doi=10.1111/j.1365-4632.2007.03520.x |pmid=18173512}}</ref>
-cite web
-| author =Ogden J, Nyblade L
-| publisher = [[International Center for Research on Women]] | year = 2005 | title = Common at its core: HIV-related stigma across contexts | url = http://www.icrw.org/docs/2005_report_stigma_synthesis.pdf | format = PDF | accessdate = 2007-02-15
-}}</ref>
-AIDS stigma has been further divided into the following three categories:
-# Instrumental AIDS stigma&mdash;a reflection of the fear and apprehension that are likely to be associated with any deadly and transmissible illness.<ref name=Herek1999>{{
-cite journal
-| author=Herek GM, Capitanio JP | journal=American Behavioral Scientist | year=1999
-| url=http://psychology.ucdavis.edu/rainbow/html/abs99_sp.pdf
-| format= PDF
-| title=AIDS Stigma and sexual prejudice
-| accessdate = 2006-03-27
-| volume=42
-| issue=7
-| pages=1130-1147
-| doi=10.1177/0002764299042007006
-}}</ref>
-# Symbolic AIDS stigma&mdash;the use of HIV/AIDS to express attitudes toward the social groups or lifestyles perceived to be associated with the disease.<ref name=Herek1999 />
-# Courtesy AIDS stigma&mdash;stigmatization of people connected to the issue of HIV/AIDS or HIV- positive people.<ref name=Snyder>{{
-cite journal |
-author=Snyder M, Omoto AM, Crain AL |
-title=Punished for their good deeds: stigmatization for AIDS volunteers |
-journal=American Behavioral Scientist | year=1999 | pages=1175&ndash;1192 | volume=42 | issue=7 | doi=10.1177/0002764299042007009
-}}</ref>
-Often, AIDS stigma is expressed in conjunction with one or more other stigmas, particularly those associated with [[homosexuality]], bisexuality, promiscuity, and [[Intravenous drug use (recreational)|intravenous drug use]].
-In many developed countries, there is an association between AIDS and homosexuality or bisexuality, and this association is correlated with higher levels of sexual prejudice such as anti-homosexual attitudes.<ref name=Herek2002>{{cite journal
-|author=Herek GM, Capitanio JP, Widaman KF
-|title=HIV-related stigma and knowledge in the United States: prevalence and trends, 1991-1999
-|journal=Am J Public Health
-|volume=92
-|issue=3
-|pages=371–7
-|year=2002
-|pmid=11867313
-|doi=
-|url=http://psychology.ucdavis.edu/rainbow/html/ajph2002.pdf
-|accessdate=2008-03-10
-}}</ref> There is also a perceived association between AIDS and all male-male sexual behavior, including sex between uninfected men.<ref name=Herek1999/>
-*'''[[Death]]'''
-The strongest risk factor for excess mortality are:
-:* Viral load more than 400 copies/mL.
-:* CD4 count less than 200 cells/mL.
-:* [[Cytomegalovirus retinitis]].
 ==References==
 {{reflist|2}}
 [[Category:HIV/AIDS]]
+[[Category:Disease]]
+[[Category:Immune system disorders]]
+[[category:viral diseases]]
+[[Category:Pandemics]]
+[[Category:Sexually transmitted infections]]
+[[Category:Syndromes]]
+[[Category:Virology]]
+[[Category:AIDS origin hypotheses]]
+[[Category:Medical disasters]]
+[[Category:Acronyms]]
+[[Category:Immunodeficiency]]
+[[Category:Microbiology]]
+{{WH}}
+{{WS}}